Method and device for production of lyophilized hydrochloride-1β, 10β-epoxy-13-dimethylamino-guaia-3(4)-en-6,12-olide

ABSTRACT

Method of producing an antitumor preparation of natural origin lyophilized arglabin 1β, 10β-epoxy-13-dimethylamino-guaia-3(4)-en-6, 12-olide hydrochloride includes resin extraction from a natural material, its purification from worthless substances, resin separation into separate components by column chromatography with production of technical arglabin. Technical arglabin further undergoes recrystallization, amination and hydrochloration at given parameters of pH solutions with production of aminoarglabin hydrochloride and its further lyophilization and high quality identification by IR-spectroscopy. A device for the realization of the method is also disclosed herein.

This application is a 371 of PCT/KZ97/00006 dated Dec. 19, 1997.

The present invention relates to pharmaceutical industry, to thesesquiterpene lactones and, particularly, to the method of production oflyophilized hydrochloride 1β,10β-epoxy-13-dimethylamino-guaia-3(4)-en-6,12-olide of the followingformula

which has antitumour activity and can be used to develop newpreparations for chemotherapy of malignant tumours.

The method of production of arglabin lyophilized having antitumouractivity from the natural material-flower baskets and leaves of endemicplant Artemisia glabella Kar. et Kir. was described in preliminarypatent of the Republic of Kazakstan, N 5277, cl.CO7D 307/93, A61K,31/365, 1997).

According to this method initially dry grinded natural material istreated by a solvent in the extractor, then extracted substances (resin)are purified from worthless products through treatment by 60% acqueoussolution of ethyl alcohol. The resin produced at the stage ofpurification is divided into separate components by the method of columnchromatography on silicogel. The said column is eluted with benzene andthe fractions containing arglabin are separated. Benzene is distilledand technical arglabin is produced which is further subjected tocrystallisation, amination and hydrochloration. In this method aminationis carried out by dimethylamine with production of a solution containingarglabin. Then the alcohol solution of aminoarglabin is barbotaged bychlorine hydride and the target product—aminoarglabin hydrochloride isproduced. Amination and hydrochloration reactions are controlled by themethods of thin layer chromotography. Technical hydrochloride ofaminoarglabin is purified by crystallization with subsequent drying andlyophilization.

Disadvantages of the above method are its rather low yield of targetproducts in the amination and hydrochloration reactions.

Different devices are used for extraction, for example, the deviceconsisting of extractor with a jacket in the extraction zone,evaporator, condenser and heater (the USSR author's certificate N1117071, cl. BO1D 11/02, 1984).

The USSR author's certificate N 670310, cl. BO1D 11/02, 1979 describesthe device for gas-liquid extraction consisting of evaporator, condenserand extractor, where the extracted mixture is heated by the heatproduced at condensation of extragent vapours transported fromevaporator, said heat is transmitted through the wall of the extractor.

The disadvantage of all these devices is periodicity of their operationwhat cannot provide high productivity. These devices also do not provideextraction of the extragent from waste material what results in greatlosses of the extragent. In the USSR author's certificate N 1117071reacting mixture is heated by an additional power supply what increasespower consumption in the process of extract production.

The USSR author's certificate N 1426611, cl. BO1D 11/00, 1988 describesthe device for extraction in the solid-liquid system consisting of thebody, extraction chamber with changeable container, evaporator andcondenser which enables to distill the extragent from the solid phase bya warm inert gas at the final stage of extraction. This device also doesnot provide continuous operation and, respectively, has lowproductivity. Besides, when volatile extragents are distilled by a warmgas while condenser is cooled by the water, the whole extragent can betaken away with the gas without its condensation in the condenser. Forexample, according to our calculations, to distill chloroform by a gaswith initial temperature 70° C. and to cool it in the condenser to 20°C., 5 m³ of gas are required for evaporation of 1 kg of chloroform andfor its condensation partial pressure of chloroform in the gas must benot lower than the saturation partial pressure at 20° C. whatcorresponds to the content of 1 kg of chloroform in 1 m³ of gas. Thus,partial pressure of chloroform in the gas in the above example is 5times lower than that required for condensation, i.e. no condensation ispossible in the condenser and all the chloroform will leave thecondenser together with the gas.

There are also some special devices for solvent removal from the wastematerial, for example, the method and device for removal of the solventfrom solid substances, consisting of a capacity for waste materialcontact with heat-carrying agent, separators for extragent andheat-carrying agent separation, condensers for extragent vapours.(Patent EPV N00356338, cl. BO1D 11/00, 1990).

Such devices are complicated and energy consuming, besides, when wastematerial is reloaded from the extraction device to other devices, it isimpossible to prevent extragent losses or it is necessary to use complexhermetic devices for reloading.

The closest to the claimed device is a section blade extractor of drynatural material of continuous operation consisting of cylindric bodydivided by partitions with openings into not less than three sections,separation and humidity chamber, shaft mounted on the same axis with thebody with reloading ladles, mixing blades and loader are attached tosaid shaft (the USSR author's certificate N 1627208, cl. BO1D 11/02,1991).

This design provides increase in productivity as compared with the abovedevices but this increase is not sufficient. The disadvantage of thisdesign is also high extragent consumption as this device does not enableto extract extragent from waste material what results in extragentlosses. The usage of other known devices to extract extragent from wastematerial considerably increases the cost of the installation andrequires additional devices providing reloading and transportation ofwet waste raw material without extragent emission to the environment.

The purpose of the present invention is to develop a method and devicewhich could provide high yield of target product, complete extraction ofthe extract from raw material, increase in productivity of theextraction device, reduction of power supply, minimization of extragentlosses, exclusion of extragent emission in the environment and, thus,guarantee of environmentally safe production.

According to the invention these tasks are solved by claims 1 and 3 ofthe claims. Preferred embodiments of the invention are given independent claims.

The method of production of lyophilized hydrochloride 1β,10β-epoxy-13-dimethylamino-guaia-3(4)-en-6,12-olide-antitumourpreparation arglabin lyophilized from endemic plant Artemisia glabellaKar.et Kir. comprises resin extraction from raw material, itspurification from worthless side substances, separation of said resininto separate components by column chromatography with production oftechnical Arglabin which is further subjected to recrystallization,amination and hydrochloration with production of aminoarglabinhydrochloride and its further recrystallization, drying, lyophilizationand high quality identification, where preferred amination is carriedout by solution of crystallic arglabin in alcohol with addition ofdimethylamine in said alcohol solution till pH of the solution reaches12.3-12.4, and where to extract aminoarglabin hydrochloride from saidsolution containing aminoarglabin alcohol is distilled and chloroform isfilled in, the remaining water is removed, said solution is filteredsaid chloroform is evaporated and alcohol added, then the solution isbarbotaged by chlorine hydrine to 5.0-5.5 pH solution, alcohol isevaporated and ethylathetate added.

It is preferable to carry out high quality identification of arglabin byIR-spectroscopy.

In the claimed method stages of amination and hydrochloration undergiven operation parameters of pH-solutions provide high yield of13-dimethylaminoalglabin and 13-dimethylaminoalglabin hydrochloridereactions. In its turn, it provides high output of target product.

The invention also includes the device to implement this method.Technical result of the present invention is achieved by the device forlyophilized arglabin extraction from natural raw material consisting ofhorizontal extractor including cylindrical body divided by partitionswith openings into not less than three sections, separation and humiditychambers, shaft mounted on the same axis with the body with reloadingladles, blade mixers and the loader attached to it, the said extractoris provided with additional section with heated walls to remove extractfrom waste material and dry waste material collector, the walls ofcontact sections are water-cooled, cavities of cooling jackets of upperparts of the walls of said section being in contact with vapour-gasmedium and lower parts of the walls being in contact with extractionmixture are not connected with each other, the system of gas circulationis connected to the extractor cavity, the said system consists of branchpipe for gas supply connected to dry waste material collector, branchpipe for gas removal connected to the cavity of the contact section ofthe extractor, low temperature condenser and ventilator, lead screwmounted in the separation chamber is connected to said shaft of theextractor and the partition between the separation and the humiditychambers is supplied with additional opening in its upper part.

According to one claim of the invention, the cylindrical body of theextractor is mounted with an inclination.

The other claim of the invention is that the branch pipe for the extractremoval from the separation chamber of the extractor is connected to thefiltering centrifuge connected in series with evaporator and condenser.

The advantage of the invention is that as compared with the knowndevices the present design provides heating of extracted mixture andkeeping of its temperature at a required level due to condensation ofextragent vapour inside the extractor and usage of condensation heat forheating of extracted mixture what results in increase in theproductivity of extraction and reduction in extragent consumption andpower supply.

The device contains preferred additional section with heated wallsdesigned to remove extragent from waste material what enables to reduceextragent losses.

The device is supplied with the system for gas circulation which removesthe air entering the extractor in the pores of raw material, and, thus,prevents emission of extragent vapours into atmosphere and excludesextragent losses, as well as removes air or other gas supplied toreplace extragent vapour in dry waste material pores before itsunloading what also reduces extragent losses.

The device provides continuous removal of not only precipitated but alsoof suspended particles from the separation chamber after purification ofthe extract before its withdrawal from the extractor.

The preferred technology provides environmentally safe operation of thedevice without extragent emission in the environment and deep gasesprecipitation from the extractor before their emission to theatmosphere.

The present extractor provides continuous process of multi-stageextraction of final product by liquid extragent with continuous mixingof extraction mixture at optimal extraction temperature and counterflowof raw material and extragent that ensures the most complete extractionof the final product out of raw material and maximal productivitywithout extragent losses. Below the invention is explained in details onthe examples of its implementation.

FIG. 1 shows the extractor, its longitudinal section. FIG. 2 shows thescheme of the device for the extraction of arglabin lyophilized from rawmaterial.

The extractor consists of a cylindric inclined body 1 divided byvertical partitions 2 and 3 into sections. Partition 4 divides the firstsection into separation 5 and humidity 6 chambers. Along the axis of thebody, the rotating shaft 7 is mounted, reloading ladles 8 and blademixers 9 are attached to it. In separation chamber 5 (sedimentator)peripheral lead screw with a small gap to the body is placed, itsinternal edge in the upper point of the extractor is dipped into liquid.In the upper part of the partition 4 the opening 11 is made, its loweredge is located at the liquid level. There is also the opening 12 in thelower part of partition 4. The loading device 13 with feeder and bin forraw materials is mounted on the humidity chamber 6 in the first sectionof the extractor. There are two openings 7 in the partitions 2, theupper opening 14 is intended for reloading of raw material to the nextsection and the lower opening 15 closed by mesh is designed forextragent transfer.

There can be one or several contact sections 16 in the extractor. In thelast section with respect to raw material motion, contact section 17,there is no opening in the partition 3 and said partition 3 ishermetically sealed in the part which is lower than the level ofextraction mixture.

On the body 1 of the extractor near contact sections 16, 17, waterjackets 18 and 19 are made. Water jacket 18 is placed higher than theextracted mixture level in the extractor and water jacket 19 is placedlower than that level. The cavities of both jackets are not connectedwith each other and have separate branch pipes for supply and dischargeof cooling water.

Next to the last contact section 17 along the raw material motion, thereis an additional section 20 (dryer) designed to remove extragent fromthe waste raw material. On the body of section 20, predominantly in itslower part being in contact with the waste material, the heater 21, forexample, an electric heater, is mounted. In section 20 the collector ofdry waste material 22 is placed, it is supplied with a hinged out window23 with a grid, the unloading port of collector 22 is closed by easilyremoved lid 24. The canal 25 is designed to supply air or inert gas toventilate waste material in the collector 22. The gas is heated, forexample, by heater 21 or a special gas heater. In the upper point of thebody 1 near the contact section 16 there is the branch pipe 26 for gasremoval from the extractor, the said branch pipe is connected with lowtemperature condenser 27 cooled by the coolant supplied by therefrigerator. The ventilator 28 is designed to draw off the gases.

The extractor operates as follows:

Dry grinded natural raw material (flower baskets and leaves of Artemisiaglabella Kar.et Kir.) is supplied through the feeder 16 into thehumidity chamber 6, where it is mixed with extragent by mixers 9. Theraw material impregnated with extragent is reloaded by reloading ladles8 through the port 14 in partitions 2 into contact section 16 where itis continuously mixed with extragent by mixers 9 and moved to the nextsection. Further the raw material is transported by reloading ladles 8to the section 17 into which the newly made extragent is supplied fromthe opposite side. In the section 17 the raw material is washed by anewly made solvent, released from the residue of the target product andby reloading ladles is transported to the section 20 where the extragentis evaporated from waste material during its contact with hot walls.Mixers 9 are used to mix the waste material and to achieve uniformdrying and to transport it to waste material collector 22 where theextragent vapour is displaced from the pores of waste material by heatedair or inert gas supplied under the grid 23. As the collector 22 isfilled, the dry ventilated waste material is discharged, to do this thegrid 23 is lowered and the lid 21 is opened. The extragent vapour flowsthrough the upper opening in partition 4 from the drying section 20 tothe section 17 where the most part of said vapour is condensed on thesurfaces cooled by water passing through the upper water jacket 18 aswell as on the surface of extracted mixture heating it. Condensedextragent flows down to the extracted extragent mixture. The residue ofextragent vapour together with the air flows through the upper openingin the partition into the contact section 16 where they are condensed topartial saturation pressure corresponding to the temperature of thevapour—gas mixture drawn off from the extractor. The temperature of theextracted mixture is regulated by the amount of cooling water suppliedto the lower water jacket 19. Gases from the extractor containing asmall amount of extragent vapours are transported through the branchpipe 26 to the low temperature condenser 27 cooled by the coolant from arefrigerator machine, in the said condensor extragent vapours are almostcompletely condensed from gases. The condensate from the condenser 27 isreturned to the extractor. The gas cleared from extragent vapours isemitted through the discharge ventilator 28 to the atmosphere. The airentering the extractor with the raw material in its pores is drawn offin the same way through the branch pipe 26.

The newly made extragent enters section 17 near the unloader of wastematerial, the condensed extragent from the drying section 20 runs downto the same place. The extragent in the reactor moves from section tosection through the lower openings 15 in the partitions in the oppositedirection to the raw material flow. Grids on these openings preventopposite motion of raw material. From the humidity chamber 6 theextragent through the lower opening in the partition 4 enters theseparation chamber 5 where it is purified, heavy particles go down andlight particles rise up and are removed by the peripheral lead screwfrom the separation chamber to the humidity chamber, suspended particlesare removed through the upper opening 11 and precipitated particles areremoved through the lower opening 12. Purified extract (extragentsaturated with extracted substances) is transported from the near-axiszone of the extractor for the further processing as it is shown in FIG.2.

According to the scheme given in FIG. 2 the extraction device consistsof continuously operating counterflow section extractor 1 withadditional section 2 with heated walls for extragent removal from wastematerial with common drive 3. The loader consisting of intermediatebunker 4, feeder 5 with drive 6 and canal 7 is mounted on the extractor.The changed capacity 8 with raw material is placed on the intermediatebunker 4, a standard craft-sack is used as changed capacity. The pump 9is intended to feed the extract from the extractor 1 to the filteringcentrifuge 10 placed on the extractor where the extract is cleared fromsuspended particles. Particles precipitated from the extract in thecentrifuge are discharged from the centrifuge to the last stage of theextractor. Then the extract is feeded to the film-type evaporator 11with built-in steam generator for condensation. The condensed extract isperiodically poured out from the condenser 11 to the changeablecapacities 12. The evaporator 11 is connected with the water-cooledcondenser 13 from which the distilled extragent is transported to thebuffer tank 19. Pure extragent is transported from the tank 19 to thelast stage of the extractor and moved to the first stage in thedirection opposite to that of the raw material flow, extracting targetsubstances from it. The tank 19 is equipped with level meter, flow meterand regulator of extragent and flow.

The extractor 1 is equipped with the system for gas removal whichconsists of condenser 14 cooled by water, freezer 15 whichsimultaneously serves as an evaporator for freon refrigerator machine,in the capacity of which the freezer of a household fridge is used, andventillator 17. Gases from the extractor are transported to thecondenser where the excess of extragent vapours, not having condensed onthe walls of the extractor, is condensed. Further, the gases enter thefreezer 15, the temperature of its walls is kept at −15-20° C. by therefrigerator machine 16, and the extragent vapours remained in gasescondense on its walls. Then gases practically completely cleared fromextragent vapours are discharged by the ventilator 17 to the commonventilation system in the building.

The worked out and dried raw material is collected into easily removedchangeable capacity 18 (a standard craff-sack).

Instruments for direction, control, regulation, signalling andprotection of the device are mounted on the control panel 20. All unitsof the device operate under low pressure what excludes penetration ofthe vapour into the premises.

The device is mounted on its own frame and does not need specialbasement. Its operation is attended by 1-2 specially trained operators.

The design of the device enables without its dismounting to completelyclean the device from the extragent without losses into the environmentand almost completely (95-98%) from raw material when the device isprepared for repairings or change of raw material or extragent.

The design of the device enables to observe its operation and readjustit without unloading of raw material or extragent and without extragentemission to the environment.

During working day 0.539 kg of resin (the total amount of extractedsubstances) is produced what amounts to 7% with respect to dry rawmaterial. The resin produced is further transported to stage II where itis purified from side substances.

For this purpose the resin is treated by 1.078 liter of ethyl alcoholheated to 60° C., the resin is solved in the said alcohol under mixing.Then heated distilled water is poured in the volume ratio of ethylalcohol to water equal to 2:1. The mixture is mixed carefully during 30minutes and kept at room temperature without mixing during 24 hours.Side substances precipitate during this time. In a 24-hour period thesedimentation is mixed by the mixer and alcohol-water solution isfiltered by vacuum. Alcohol as an azeothropic mixture with watercontaining 68-70% of alcohol is distilled from the obtained filteredsubstance under vacuum and at temperature of 50-52° C. The yield ofresin amounts to 286 g.

In stage III the resin produced in stage II is divided into individualcomponents by column chromatography. Benzene is fed under pressure inthe column and benzene fraction containing arglabin is separated. Thepresence of arglabin in the benzene fraction is determined by the methodof thin layer chromatography on Silufol plates. After benzene distillingfrom fractions, there remains technical arglabin with an admixture ofyellow oil amounting to 33.1 g what equals to 11.7% of the processedresin.

Stage IV is a process of arglabin recrystallization. For this, technicalarglabin is dissolved in hexane while heating on water bath at the ratioof product (kg)-solvent (1) equal to 1:10 and filtered under vacuum.During cooling to room temperature the crystals of arglabin start toisolate from the filtrate. After complete hexane removal, arglabin yieldamounts to 21 g (63%).

At stages V and VI arglabin is aminated and hydrochlorated. To produceaminoarglabin, crystallic arglabin is dissolved in alcohol. Thendimethylamine is added to the alcohol solution till bringing pH to12.3-12.4. Then alcohol is distilled from the solution containingaminoarglabin and chloroform is poured in. The main part of the water isseparated by separating funnel. Traces of the remaining water areremoved by one of the dryers (MgSO₄ or Na₂SO₄) till total transparencyis achieved, the duration of treatment is about 12-14 hours. Thesolution is filtered, chloroform is evaporated and alcohol is added.Then said solution is barbotaged by chlorine hydride till pH reaches5.0-5.5. Alcohol is evaporated from the solution and ethylacetate isadded. The crystals of 13-dimethylaminoarglabin hydrocholide areprecipitated. Its yield is 105%. The solution is evaporated till dry andtechnical aminoarglabin hydrochloride in the form of a powder isproduced.

At stage VII aminoarglabin hydrochloride (technical product) is purifiedby fractional recrystallization. The product is dissolved in chloroform,then said chloroform is removed on rotatory evaporator. Under intensivestirring ethylacetate is added to the remained resin. The precipitatedsedimentary of aminoarglabin hydrochloride is filtered throughvacuum-pistol and used for the production of arglabin-lyophilizedpreparation. The yield of arglabin-lyophilized (target product) is 20 g(95% at this stage).

At the last stage VIII the produced target product is dried overanhidrone under vacuum, dissolved with apyretic distilled water atratio: 2 g of dry substance per 100 ml of water. The produced solutionis lyophilized by one of the following methods.

Method 1. Produced aqueous solution is passed through cotton-gauzetampon in the tank with Millipor filter. The solution is filteredthrough sterile Millipor trimmed by filtering plates into a sterileglass vessel. Then the solution is pumped by means of vacuum from theglass vessel into a measuring burette from which it is poured into 2 mlbottles and dried in lyophilizer KS-30. To do this the bottles areplaced on trays. When the trays are filled with bottles, they arewrapped into a sterile sheet and placed on freezing counter forhardening at −40° C. for not less than 24 hours. After this proceduredrying is commenced. In 2 hours after the beginning of drying, heatingof the shelves is turned on. The shelves are heated gradually up to+50±5° C. The product turns from negative to positive temperature at12th-13th hour of drying. The final temperature of the product shouldnot exceed +60° C.

Duration of drying is 24 hours. After the lyophilic drying, the bottleswith preparation are immediately closed by the corks, covered by capsand rolled. Each bottle contains 0.04 g (0.00004 kg) of preparation.

Method 2. Aqueous solution is filtered through cotton-gauze tampon or 8layers of gauze, poured into 2 ml bottles or ampules and lyophilizedunder the above conditions. The bottles with dry preparation areimmediately closed by the corks, covered with caps and rolled. Ampulesare soldered. Bottles or ampules with preparation are packed up in bicksor double-layered sacks and sterilized in autoclave during 20 minutes atthe pressure of 1.2 Atm and temperature 120° C. Each bottle (ampula)contains 0.4 g (0.00004 kg) of the preparation.

Method 3. Prepared aqueous solution is filtered through cotton-gauzetampon or 8 gauze layers, poured by 200 ml into flasks of volume of 500ml, closed by cotton-gauze tampons and tied up by oil-paper. The flaskswith solution are sterilized in autoclave during 30 minutes at 1.2 Atmand the temperature of 120° C. The sterile solution is cooled to roomtemperature, sterily poured by 2 ml into the bottles with the volume of10 ml and dried in the lyophilizer as stated above. Afterlyophilization, each bottle contains 0.04 (0.00004 kg) of preparation.

The yield of preparation is 17 g what amounts to 88.2% at this stage and0.22% with respect to air-dry natural material. Arglabin lyophylizedpreparation is a straw-white compound with a bitter taste.

According to the present invention high qualitative identification ofarglabin lyophilized is made by IR-spectroscopy. Spectrum of 1% ofstandard arglabin sample solution in chloroform is analysed byIR-spectrometer. The spectrum has characteristic absorption lines at2800, 1775, 1650 cm⁻¹.

The 1775 cm⁻¹ line is characteristic for carbonyl group of γ-lactone andit does not overlap with other spectrum lines, therefore it is used tocalculate the coefficient of absorption for the solution of a standardarglabin sample.

The coefficient of absorption is calculated by the formula:$a = \frac{A}{c_{1} \cdot c_{2} \cdot b}$

where A is an optical density;

c₁ is a fraction of investigated compound in the sample; %

c₂ is sample concentration in the analysed solution, %;

b is the thickness of cuvette, mm.

Content of arglabin in the standard sample is equal to 100%.Concentration of the sample in the analysed solution is 1%, cuvettethickness is 0.4 mm.$a = {\frac{0.9852}{(1) \cdot (100) \cdot 0.4} = 0.02463}$

To make quantitative estimation, IR-spectrum of arglabin solution inchloroform with known concentration is measured. The band width of T %at 1775 cm⁻¹ is transformed into optical density and arglabinconcentration is calculated by the formula:$C_{2} = \frac{A}{a \cdot b \cdot c_{1}}$

Percentage concentration of arglabin is determined by spectrophotometerand it is not less than 99.9%.

The control of the quality of preparation can also be made by the methodof thin layer chromatography, qualitative reaction of preparationinteraction with solution in sulphuric acid, determination of meltingtemperature, specific rotation.

Antitumour activity and toxicity of the substance and medicinal form ofthe present preparation of dimethylaminoarglabin hydrochloride wasdetermined according to the commonly used techniques.

Thus, the present method and device enable to produce highly-effectiveantitumour preparation of the natural origin-arglabin lyophilisedpossessing high antitumour and immuno-stabilizing activity andrelatively low toxicity.

What is claimed is:
 1. A method of production of lyophilizedhydrochloride 1β, 10β-epoxy-13-dimethyl amino-guaia-3(4)-en-6, 12-olidefrom endemic plant Artemsia glabella Kar. et Kir. including resinextraction from the initial product, its purification from worthlesssubstances, said resin separation into separate components by the methodof column chromatography with production of technical arglabin which isfurther subjected to recrystallisation, amination and hydrochlorationwith production of aminoarglabin hydrochloride and its furtherrecrystallisation, drying, lyophilisation and high qualitativeidentification in which: said amination is carried out by solvingcrystalline arglabin in alcohol with addition of dimethylamine to thesaid solution till pH of said solution reaches 12.3-12.4, at theprevious stage to extract aminoarglabin hydrochloride containingaminoarglabin, alcohol is distilled and chloroform is filled in, theremaining water is removed, said solution is filtered, said chloroformis evapored and alcohol added, the said solution is barbotaged bychlorine till pH of the solution reaches 5.0-5.5, said alcohol isevapored and ethylacetate is added.
 2. The method as claimed in claim 1,wherein said high quality identification of lyophilised arglabin iscarried out by means of IR-spectroscopy.
 3. A device for the extractionof arglabin lyophilised from natural material consisting of horizontalextractor including cylindrical body divided by partitions with openingsinto not less than three sections, separation and humidity chamber, theshaft mounted on the same axis with said body, ladles and blade mixersattached to said shaft, and the loader, in which the said extrator issupplied with an additional section with heated walls to remove theextract from waste material and collector of dry waste material, thewalls of contact sections are water cooled, the cavities of coolingjackets in the upper parts of the walls, being in contact withvapour-gas medium, and in the lower parts of the walls, being in contactwith the extracted mixture, are not open to each other, said system ofgas circulation is connected to said extractor cavity, said system forgas supply includes branch pipe connected to the cavity of contactsection of the extractor, low temperature condenser and ventilator, thelead screw placed in the separation chamber is connected to the shaft ofthe extractor, the partition between the separation and the humiditychambers is made with additional opening in its upper part.
 4. Thedevice as claimed in claim 3, the cylindrical body of the extractor isinclined.
 5. The device as claimed in claim 3, wherein the branch pipefor removing the extract from the separation chamber of the extractor isconnected to a filtration centrifuge which is connected with anevaporator and condenser in series.